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A cytogenetic study of hospital workers occupationally exposed to radionuclides in Serbia: premature centromere division as novel biomarker of exposure?

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Abstract

Purpose

The health risk of chronic exposure to radionuclides includes changes in the genome (e.g., chromosomal aberrations and micronuclei) that increase chromosomal instability. There are also other phenomena, which seem to appear more frequently in metaphases of exposed persons (such as premature centromere division). The aim of this study was to discover whether or not there is correlation between incidence of named cytogenetic changes in persons occupationally exposed to radionuclides in comparison with unexposed control group, and if significant correlation is determined, can premature centromere division be consider as a biomarker of radiation exposure?

Methods

The exposed group comprised 50 individuals occupationally exposed to radionuclides. The reference control group consisted of 40 unexposed individuals. Chromosomal aberrations, micronuclei and premature centromere division were analyzed according to a standard International Atomic Energy Agency protocol. Statistical analyses were performed using SPSS 17.0 statistics.

Results

The means for analyzed cytogenetic changes were significantly higher in the exposed group. Positive correlation between them was found in exposed group. Premature centromere division parameter PCD5-10 was selected as particularly suitable for separating groups (exposed/unexposed).

Conclusions

Identification of other phenomena related to radionuclide exposure, beside well known, may clarify recent problems in radiobiology concerning the biological response to low doses of ionizing radiation and its consequences.

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References

  • Ainsbury EA, Bakhanova E, Barquinero JF, Brai M, Chumak V, Correcher V et al (2011) Review of retrospective dosimetry techniques for external ionising radiation exposures. Radiat Prot Dosim 147(4):573–592

    Article  CAS  Google Scholar 

  • Antunes AC, Martins V, Cardoso J, Santos L, Monteiro Gil O (2014) The cytokinesis-blocked micronucleus assay: dose estimation and inter-individual differences in the response to γ radiation. Mutat Res 760:17–22

    Article  CAS  Google Scholar 

  • Ballardin M, Antonelli A, Cipollini M, Fallahi P, Scarpato R, Tomei A et al (2007) Induction of chromatid-type aberrations in peripheral lymphocytes of hospital workers exposed to very low doses of radiation. Mutat Res 626(1–2):61–68

    Article  CAS  Google Scholar 

  • Barquinero JF, Barrios L, Caballin MR, Miro R, Subias A, Egozeue J (1993) Cytogenetic analyses of lumphocytes from hospital workers occupationally exposed to low levels of ionizing radiation. Mutat Res 286(2):275–279

    Article  CAS  Google Scholar 

  • Bigatti P, Lamberti L, Ardito G, Armellino F (1988) Cytogenetic monitoring of hospital workers exposed to low-level ionizing radiation. Mutat Res 204(2):343–347

    Article  CAS  Google Scholar 

  • Bonassi S, Forni A, Bigatti P, Canevarolo N, De Ferrari M, Lando C et al (1997) Chromosome aberrations in hospital workers: evidence from surveillance studies in Italy (1963–1993). Am J Ind Med 31(3):353–360

    Article  CAS  Google Scholar 

  • Bouraoui S, Mougou S, Drira A, Tabka F, Bouali N, Mrizek N et al (2013) A cytogenetic approach to the effects of low levels of ionizing radiation (IR) on the exposed Tunisian hospital workers. Int J Occup Med Environ Health 26:144–154

    Article  Google Scholar 

  • Broccoli D, Paweletz N, Vig BK (1989) Sequence of centromere separation: characterization of multicentric chromosomes in a rat cell line. Chromosoma 98(1):13–22

    Article  CAS  Google Scholar 

  • Bühler EM, Fessier R, Beutler C, Gargano G (1987) Incidental finding of double minutes (DM), single minutes (SM), homogenously staining regions (HSR), premature chromosome condensation (PCC) and premature centromere division (PCD)? Ann Genet (Paris) 30:75–79

    Google Scholar 

  • Engin AB, Ergum MA, Yurtcu E, Kan D, Sahin G (2005) Effect of ionizing radiation on the pteridine metabolic pathways and evaluation of its cytotoxicity in exposed hospital staff. Mutat Res 585:184–192

    Article  CAS  Google Scholar 

  • Fenech M, Bonassi S (2011) The effect of age, gender, diet and lifestyle on DNA damage measured using micronucleus frequency in human peripheral blood lymphocytes. Mutagenesis 26(1):43–49

    Article  CAS  Google Scholar 

  • German U, Ben-Shachar B, Weinstein M (2000) Twenty five years of TL-dose measurements at the NRC-NEGEV. In: Proceedings of IRPA-10; Hiroshima, Japan: International Radiation Protection Assocation: CD ROM paper p3b–168

  • Gollin SM (2005) Mechanisms leading to chromosomal instability. Semin Canc Biol 15:33–42

    Article  CAS  Google Scholar 

  • Hoeijmakers JHJ (2001) Genome maintenance mechanisms for preventing cancer. Nature 411:366–374. doi:10.1038/35077232

    Article  CAS  Google Scholar 

  • International Atomic Energy Agency (IAEA) (2001) Cytogenetic analysis for radiation dose assessment. International Atomic Agency Technical Report Series 405. Vienna: IAEA

  • Jovičić D, Milačić S, Milić N, Bukvić N, Vukov DT (2009) Chromosomal aberrations in subjects exposed to ionizing radiation. J Environ Pathol Toxicol Oncol 28:75–82

    Article  Google Scholar 

  • Jovičić D, Milačić S, Vukov TD, Rakić B, Stevanović M, Drakulić D et al (2010) Detection of premature segregation of centromeres in persons exposed to ionizing radiation. Health Phys 98:717–727

    Article  Google Scholar 

  • Ko M, Lao XY, Kapadia R, Elmore E, Redpath JL (2006) Neoplastic transformation in vitro by doses of ionizing radiation: role of adaptive response and bystander effects. Mutat Res 597:11–17

    Article  CAS  Google Scholar 

  • Litmanovic T, Altras MM, Dotana A, Avivi L (1998) Asynchronous replication of homologous alfa-satellite DNA loci in man is associated with nondisjunction. Cytogen Cell Genet 81:26–35

    Article  Google Scholar 

  • Madan K, Lindhout D, Palan A (1987) Premature centromere division (PCD): a dominantly inherited cytogenetic anomaly. Hum Genet 77:193–196

    Article  CAS  Google Scholar 

  • Maffei F, Angelini S, Forti GC, Lodi V, Violante FS, Mattioli S et al (2002) Micronuclei frequencies in hospital workers occupationaly exposed to low levels of ionizing radiation: influence of smoking status and other factors. Mutagenesis 17(5):405–409

    Article  CAS  Google Scholar 

  • Major J, Jakab MG, Tompa A (1999) The frequency of induced premature centromere division in human populations occupationally exposed to genotoxic chemicals. Mutat Res 445:241–249

    Article  CAS  Google Scholar 

  • Matsuura S, Ito E, Tauchi H, Kenshi K, Ikeuchi T, Tadashi K (2000) Chromosomal instability syndrome of total premature chromatid separation with mosaic variegated aneuploidy is defective in mitotic-spindle checkpoint. Am J Hum Genet 67:483–486

    Article  CAS  Google Scholar 

  • Michor F, Iwasa Y, Vogelstein B, Lengauer C, Nowak MA (2005) Can chromosomal instability initiate tumorigenesis? Rev Semin Canc Biol 15:43–49

    Article  CAS  Google Scholar 

  • Miller JH, Jin S, Morgan WF, Yang A, Wan Y, Aypar U et al (2008) Profiling mitochondrial proteins in radiation-induced genome-unstable cell lines with persistent oxidative stress by mass spectrometry. Radiat Res 169(6):700–706. doi:10.1667/RR1186.1

    Article  CAS  Google Scholar 

  • Morgan WF (2003) Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro. Radiat Res 159(5):567–580

    Article  CAS  Google Scholar 

  • Morgan WF, Day JD, Kaplan MI, McGhee EM, Limoli CL (1995) Genomic instability induced by ionizing radiation. Radiat Res 146:247–258

    Article  Google Scholar 

  • Mothersill C, Seymour CB (2004) Radiation-induced bystander effects-implications for cancer. Nat Rev Cancer 4(2):158–164

    Article  CAS  Google Scholar 

  • Nefic H, Handzic I (2013) The effect of age, gender, and lifestyle factors on micronucleus frequency in peripheral blood lymphocytes of the Bosnian population. Mutat Res 753:1–11

    Article  CAS  Google Scholar 

  • Preston RJ (2005) Bystander effects: genomic instability, adaptive response and cancer risk assessment for radiation and chemical exposures. Toxicol Appl Pharmacol 207:550–556

    Article  Google Scholar 

  • Resta N, Susca FC, Di Giacomo MC, Stella A, Bukvic N, Bagnulo R et al (2006) Homozygous frameshift mutation in the ESCO2 gene: evidence of intertissue and interindividual variation in Nmd efficiency. J Cell Physiol 209:67–73

    Article  CAS  Google Scholar 

  • Ropolo M, Balia C, Roggieri P, Lodi V, Nucci MC, Violante FS et al (2012) The micronucleus assay as biological dosimeter in hospital workers exposed to low doses of ionizing radiation. Mutat Res 747(1):7–13. doi:10.1016/j.mrgentox.2012.02.014

    Article  CAS  Google Scholar 

  • Rozgaj R, Kosuba V, Simic DT (2002) The frequency of dicentrics and acentrics and the incidence of rogue cells in radiation workers. Mutagenesis 17:135–139

    Article  CAS  Google Scholar 

  • Ruskovsky SR, Petrenko YW, Bezrukov VF (2003) Premature centromere division as a biomarker of genotoxic influences. In: abstract book of the sixth international symposium and exibition on environmental contamination in Central and Eastern Europe and the commonwealth of independent status. Prague, Czech Republic, pp 1–4

  • Saberi A, Salari E, Latifi SM (2013) Cytogenetic analysis in lymphocytes from radiation workers exposed to low levels of ionizing radiation in radiotherapy, CT-scan and angiography units. Mutat Res 750(1–2):92–95. doi:10.1016/j.mrgentox.2012.10.001

    Article  CAS  Google Scholar 

  • Sankaranarayanan K, Taleei R, Rahmanian S, Nikjoo H (2013) Ionizing radiation and genetic risks. XVIII. Formation mechanisms underlying naturally occurring DNA deletions in the human genome and their potential relevance for bridging the gap between induced DNA double-strand breaks and deletions in irradiated germ cells. Mutat Res 753:114–130

    Article  CAS  Google Scholar 

  • Sari-Minodier I, Orsière T, Auquier P, Martin F, Botta A (2007) Cytogenetic monitoring by use of micronucleu assay among hospital workers exposed to low doses of ionizing radiation. Mutat Res 629(2):111–121

    Article  CAS  Google Scholar 

  • Shueller MG, Higgins A, Rudd MK, Gustashaw K, Willard HF (2001) Genomic and genetic definition of functional human centromere. Science 294:109–115

    Article  Google Scholar 

  • Spremo-Potparevic B, Zivkovic L, Djelic N, Bajic V (2004) Analysis of premature centromere division (PCD) of the X chromosome in Alzheimer patients through cell cycle. Exp Gerontol 39:849–854

    Article  CAS  Google Scholar 

  • Stephan G, Pressl S (1999) Chromosomal aberrations in peripheral lymphocytes from healthy subjects as detected in the first cell division. Mutat Res 446:231–237

    Article  CAS  Google Scholar 

  • Thierens H, Vral A, Morthier R, Aousalah B, De Ridder L (2000) Cytogenetic monitoring of hospital workers occupationally exposed to ionizing radiation using micronucleus centromere assay. Mutagenesis 15(3):245–249

    Article  CAS  Google Scholar 

  • Touil N, Aka PV, Buchet JP, Thierens H, Kirsch-Volders M (2002) Assesment of genotoxic effects related to low level exposure to ionizing radiation using biomarkers for DNA damage and repair. Mutagenesis 17(3):223–232

    Article  CAS  Google Scholar 

  • Ullrich RL, Ponnaiya B (1998) Radiation-induced instability and its relation to radiation carcinogenesis. Int J Radiat Biol 74(6):747–754

    Article  CAS  Google Scholar 

  • Vig BK (1984) Sequence of centromere separation: orderly separation of multicentric chromosomes in mouse L-cells. Chromosoma 90:39–45

    Article  CAS  Google Scholar 

  • Vig BK, Wodnicki J (1974) Separation of sister centromeres in some chromosomes from cultured human leukocytes. J Hered 65:149–152

    CAS  Google Scholar 

  • Vig BK, Zinkowski RP (1986) Sequence of centromere separation: a mechanism for orderly separation of dicentrics. Cancer Genet Cytogenet 22:347–359

    Article  CAS  Google Scholar 

  • Vig BK, Keith L, Sternes L, Paweletz N (1989) Centromere structure and function in neoplasia. Cancer Genet Cytogen 43:151–178

    Article  CAS  Google Scholar 

  • Way JS, Willard HF (1987) Nucleotide sequence heterogeneity of alpha satellite repetive DNA: a survey of alphoid sequences from different human chromosomes. Nucl Acid Res 15:7549–7569

    Article  Google Scholar 

  • Willard HF (1985) Chromosome specific organization of human satellite DNA. Am J Hum Genet 37:524–532

    CAS  Google Scholar 

Download references

Acknowledgments

We express thanks to all donors who kindly gave their blood to perform this study. We also acknowledge Ana and Ivan Sreckovic for technical support in processing of the manuscript and figures.

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Authors and Affiliations

  1. Biodosimetry Department, Serbian Institute of Occupational Health “Dr Dragomir Karajovic”, Radiation Protection Center, Deligradska 29, 11 000, Belgrade, Serbia

    Jelena Pajic, Boban Rakic & Aleksandar Milovanovic

  2. Genotoxicology Department, Faculty of Applied Ecology “Futura”, University “Singidunum”, Pozeska 83a, Belgrade, Serbia

    Dubravka Jovicic

  3. Occupational Health Department, Faculty of Medicine, University of Belgrade, Dr Subotica 8, Belgrade, Serbia

    Aleksandar Milovanovic

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  1. Jelena Pajic
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  2. Boban Rakic
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  4. Aleksandar Milovanovic
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Correspondence to Jelena Pajic.

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Pajic, J., Rakic, B., Jovicic, D. et al. A cytogenetic study of hospital workers occupationally exposed to radionuclides in Serbia: premature centromere division as novel biomarker of exposure?. Int Arch Occup Environ Health 89, 477–484 (2016). https://doi.org/10.1007/s00420-015-1086-2

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  • DOI: https://doi.org/10.1007/s00420-015-1086-2

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